Idiopathic intracranial hypertension was previously considered a rare condition, however, its prevalence is increasing in parallel with obesity in patient populations.
Historically, acetazolamide has been used as prophylaxis for altitude sickness and as an adjunct treatment for glaucoma;1 however, there is an emerging trend in health care for the off-label use of acetazolamide. This off-label use can be found in all age groups to treat idiopathic intracranial hypertension (IIH).1
IIH, formerly known as pseudotumor cerebri, was previously considered a rare condition with an incidence of 1 in 100,000 people; however, its prevalence is increasing in parallel with obesity in patient populations.2 IIH is a condition that presents with symptoms such as persistent headaches, eye pain, double vision, vision loss, and pulsatile tinnitus.2 Patients often describe other symptoms, such as flashes of light in the field of vision and a consistent “swishing” or “heartbeat” sound in the ears.
Clinical presentation of IIH includes optic-disc swelling (papilledema), visual field loss, and patient-reported symptoms with unknown causes.3 A neuro-ophthalmologist typically makes a definitive diagnosis using MRI brain imaging and lumbar puncture to rule out other causes such as malignancies, inflammatory disorders, and infections such as meningitis.4,5
The DANDY diagnostic criteria (Table 1) includes the presence of papilledema with elevated cerebral spinal fluid (CSF) opening pressure of more than 250 mm of water in adults and 280 mm of water in children and adolescents.6 In addition to ruling out cranial nerve abnormalities, abnormal brain parenchyma, abnormal CSF constituents, and other potential causes such as lesions, infections, malignancies, and hydrocephaly.5
The goal of treatment is to regain baseline patient vision and alleviate symptoms, which requires aggressive treatment to preserve vision upon diagnosis and prevent further worsening of the visual field (Figure 1).
The current drug of choice, by the Neuro-Ophthalmology Research Disease Investigator Consortium, is acetazolamide with an adult starting dose of 500 mg twice daily and titrated up, based on patient tolerance, to a maximum of 4 grams in divided doses daily.4 Children’s dosing typically starts at 25 mg/kg per day in divided doses, and is titrated slowly to a maximum of 100 mg/kg per day or 2 grams per day, whichever is less.4
Precautions for acetazolamide include patient anaphylaxis-type reactions to sulfa medications and concomitant use with interacting medications.1 Contraindications include uncontrolled electrolyte imbalances, untreated or severe adrenal insufficiency, closed-angle glaucoma, hepatic disease, renal disease, and renal failure.1
Recommended monitoring parameters for patients include comprehensive metabolic panels, visual field tests, optic disc, and nerve imaging (optical coherence tomography) on a frequent yet clinician-specific basis.6
Upon receipt of a high-dose acetazolamide prescription, the first action item for a pharmacist is to check the prescription for a diagnosis or diagnosis code. If a diagnosis is not provided, calling the patient to receive an indication for use may clarify the dose; however, if the patient is unsure of the indication, contacting the physician is warranted.
When contacting the physician, asking for an accompanying diagnosis and an escalating titration schedule, especially for treatment-naive patients, is recommended.7 Due to adverse effect (AE) occurrence, it is highly recommended to titrate acetazolamide slowly to prescribed and tolerated doses.7
The most common AEs reported with acetazolamide are abnormal sensations, numbness, and tingling, referred to as paresthesia, nausea, fatigue, headache, and changes in taste.1 If a patient is experiencing intolerable AEs, it is recommended to contact the physician, slowly titrate down, and a new patient appointment may be needed.7
Hypokalemia can also occur with acetazolamide, especially at high doses or in combination with other treatment medications, such as furosemide or topiramate.1 Common symptoms of hypokalemia can be remembered by the “6 Ls” mnemonic, including lethargy, leg cramps, limp muscles (hypotonia or weakness), lots of urine (polyuria), lethal cardiac arrest or arrhythmia, and low (or shallow) respirations.8,9
If a patient is describing or showing signs and symptoms of hypokalemia, the patient should be immediately referred to emergency medical care for appropriate blood labs and organ function monitoring. Additional recommendations for high-dose acetazolamide or new acetazolamide treatment are to inquire into a history of drug allergies, especially sulfa allergy, and a history of hepatic or renal dysfunction.
Electrolyte imbalance, acid/base disorders, weight/appetite, and neurologic symptoms are also essential to monitor for all patients taking acetazolamide.1 Some symptoms of these conditions include, but are not limited to, changes in heart rate, confusion, dizziness, fatigue or weakness, loss of appetite, headache, changes in respiration, or mood changes. If any of these signs and symptoms occur, are persistent, or concerning in any way, contact the physician immediately.10
After introductions and patient identity confirmation, ensure the patient understands the indication for the medication. Verify the provider has completed baseline lab work, including electrolytes, renal, and liver function. Usually, medication counseling can proceed once these precautions are taken and the dosing titration schedule can be reviewed.1
Best practices for counseling include adherence assistance, plus offering auto refills, discussing how and when it is easiest to remember to take the medication, and ensuring the patient can easily swallow the tablets or capsules, which can be large in size. Review AEs and precautions while emphasizing the importance of adequate hydration, especially in the summer and with exertion, and low sodium diet.
The recommendation for water intake of adult non-pregnant women is 2.7 liters (91 ounces) daily and 3.7 liters (125 ounces) for men daily.13 Recommendations for a low sodium diet in adults is less than 2.3 grams/day and children’s recommendations vary depending on the reference, therefore, physician preference should be followed.14
Although acetazolamide is not contraindicated if a patient is allergic to sulfa-based medications without previous anaphylaxis, discuss the possibility but limited likelihood of a reaction.1 Signs and symptoms of anaphylaxis include, but are not limited to, hives, hypotension, respiratory distress, or significant swelling of the tongue or lips.15
Update all allergies and health conditions in the patient’s profile to ensure that future prescriptions will flag precautions in your software. IIH is a complex condition with limited medication for treatment. The top priority is to preserve your patient’s vision.
Ultimately, the better you know your patients, the more you can prevent medication-related problems and improve adherence. As always, trust your mental red flags, and if you feel uncomfortable with a prescription, follow through, gather more information, and always document your counseling and interventions.
About the Authors
K. Ashley Garling, PharmD, clinical assistant professor, The University of Texas at Austin College of Pharmacy.
Christina Crawford, PharmD, pharmacist-in-charge, H-E-B Pharmacy.